Abstract

Background

Pembrolizumab is a monoclonal antibody against programmed cell death 1 (CD279; PD-1), recently approved by the FDA as a 2nd line therapy in NSCLC with a companion diagnostic (PD-L1 22C3, Dako). Today, the only validated IHC platform for PD-L1 detection is the Link-48 platform (Dako), which lowers the availability of the test. Ventana's benchmark XT platform is a widespread IHC platform. However, data about its reliability and reproducibility using the 22C3 antibody is lacking.

Methods

A comprehensive calibration of the 22C3 PD-L1 staining on the Benchmark XT platform (Ventana) was performed by combining the FDA-approved, pre-diluted 22C3 anti PD-L1 primary antibody (Dako) with two of Ventana's DAB detection systems, UltraView and OptiView. After receiving a comparable IHC pattern, 41 NSCLC random cases were independently evaluated by 2 expert pathologists for PD-L1 protein expression, using both platforms, defining the tumor proportion score (TPS): the percentage of tumor cells showing complete or partial membrane staining. Each case was classified as PD-L1 negative, weakly positive, or strongly positive (

Results

Using the Dako IHC platform 8, 7 and 26 cases were stratified as PD-L1 strongly positive, weakly positive and negative cases, respectively. Using the Ventana's UltraView protocol 36/41 cases (87.8%) had the same results, including the 8 strongly positive cases. Pearson's correlation score indicate a high concordance (0.91; p value

Conclusions

Pembrolizumab treatment for NSCLC patients is coupled to the PD-L1 TPS by Dako. The Ventana's benchmark XT platform can also be used safely to stratify patients with the same algorithm. We provide a defined PD-L1 IHC protocol which is easy to replicate as we used commercially available pre-made reagents only.